Lecture: Ocular Motility II

This is the second of two lectures designed to improve the participants ability to evaluate the patient with double vision. Brainstem syndromes, thyroid eye disease, myasthenia gravis and miscellaneous conditions are discussed.

Lecturer: Dr. Karl Golnik

Transcript

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DR KARL GOLNIK: All right. Greetings. This is Dr. Karl Golnik. I’m just trying to get into my slide show mode here. Here we go. Hopefully you’re seeing my title slide of ocular motility IE, brain stem, orbit, and neuromuscular junction. In part I, we covered mostly oculomotor cranial nerve palsy. So in part 2 we’ll be covering everything else, and my objectives are that when you’re done, you’ll be able to describe and illustrate common brain stem ocular motility syndromes, be able to describe and illustrate orbital causes of motility deficits, and illustrate various ocular manifestations of myasthenia gravis. So this is a cartoon from the Far Side. A bunch of dinosaurs saying time for our weekly brain stem storming session. So we’ll start with this gentleman who has double vision. You’ll see his eye movements. And this is a polling question, so there will be a poll. And you can choose with your keyboard the correct answer. And so you’ll see him trying to look to the right. And left. And right again. I think I showed that he has good vertical eye movements. Here we are. The video is repeating. So his vertical eye movements are good. But there is a problem. And the question — and hopefully you’re voting, and we’re polling here — is — yes, what does this represent? Is this myasthenia gravis, third nerve palsy, internuclear ophthalmoplegia, or Graves’ disease? And so I will let you vote for just a little longer. This is, I guess, somewhat — doesn’t necessarily hit you over the head, depending on how much eye movement stuff you look at. Let me go ahead. Thank you. So half of you indeed got the correct answer. This is an internuclear ophthalmoplegia. Some of you said myasthenia, which it certainly could be. And we’ll talk about that later. Myasthenia could mimic any problem of alignment or ophthalmoplegia. This could be a problem of alignment. We’re seeing a moderate left adduction deficit. But if you look at the abducting eye, the right eye, you’ll see there’s some abducting nystagmus. Those are the two things we look for with an INO. A contralateral abducting nystagmus — you can see it right there. There’s a few beats of it. So this is an internuclear ophthalmoplegia. And an INO is again characterized by an ipsilateral adduction deficit, contralateral abducting nystagmus. There may or may not be a vertical misalignment. We call that a skew deviation. We’ll talk about skew deviations in a moment or so. When I say nystagmus, I don’t mean the abducting nystagmus. Sometimes you’ll see a conjugate torsional nystagmus in the setting of an INO, and if you see that, you quickly know there’s got to be a brain stem problem and it’s not myasthenia mimicking an INO. So the relevant anatomy is shown on this schematic. Where there’s a problem with the medial longitudinal fasciculus, which contains the interneurons from the third nerve neurons — sorry, the neurons that run from the PPRF and the 6th nerve nucleus up to the medial rectus, subnucleus of the third nerve nucleus, and then to the medial rectus muscle. And that’s why you have this INO. You could see an isolated adduction deficit with a third nerve palsy, but that would be very rare, and in fact, in almost 30 years of neuroophthalmology, I’ve never seen an isolated medial rectus abnormality. So when you see that, think about INO, brain stem, and clearly you’re gonna get an imaging study. In a young person, you’re gonna be thinking about demyelinating disease. I guess depending on where you live in the world. And in an older person, a lacunar stroke or infarct, typically in the pons. And here’s a schematic in the pons, showing the MLFs. Right, center here. Side by side. And the small lesion here. An MS plaque. A lacunar infarct can cause a unilateral internuclear ophthalmoplegia. In the patient we just saw, it was a left INO. Here’s another woman who is exotropic. Here she is, trying to look to the left, up, she’s got a little bit of that conjugate nystagmus. And here she is in right gaze, with the abducting nystagmus, left gaze… So she’s got a bilateral internuclear ophthalmoplegia. Good vertical eye movements. But striking bilateral adduction deficits, and when she looks up in just a moment, watch the fine vertical nystagmus. See it? Tells us this is brain stem. This is not myasthenia mimicking a bilateral INO, which I have seen. So sometimes this is termed walleyed bilateral internuclear ophthalmoplegia. Here’s another patient with a much more subtle problem, a younger guy. You notice he doesn’t quite have full adduction of the left eye, but when he looks quickly from side to side, he has slow bilaterally — slow adduction. It’s hard to see. You’ve got to sit back and watch the eyes move from side to side. And you’ll see that the adducting eye, when he tries to saccade, a rapid eye movement, the adducting eye is not as fast. This can be subtle. But he’s got bilateral INOs. They’re mild. Sometimes people call them saccadic. Left INO more striking than the right. In a young patient, in the United States, this is almost always multiple sclerosis. Again, a very small lesion can affect both medial longitudinal fasciculi, giving that bilateral internuclear ophthalmoplegia. Here’s another patient with a different brain stem syndrome. And I’m gonna play this. And you’ll see here — attempting to look left, which looks pretty good. And here she is, trying to look right. So in the case where neither eye moves in a certain direction, we call that a gaze palsy. You would not use the term unilateral gaze palsy, or a left upgaze palsy. Gaze palsy, by definition, means neither eye is moving in a certain direction. In her case, she has a right gaze palsy. So when you use the term gaze palsy, you mean neither eye is moving in the direction in question. So in this patient, a right gaze palsy. And this can be due — again, here’s our cross section through the pons. So we have the medial longitudinal fasciculi. The 6th nerve nucleus, the PPRF, the paramedian pontine reticular formation. Thought of as the horizontal gaze center. But the 6th nerve nucleus is part of that. And a small lesion in the 6th nerve nucleus can cause an ipsilateral horizontal gaze palsy. So a nuclear 6th nerve lesion doesn’t just give you a 6th nerve palsy. Because of the interneurons that run from the PPRF through the 6th nerve nucleus. You can also have a lesion right in the PPRF, causing a unilateral horizontal gaze palsy. And sometimes I’ll see a lesion that affects the PPRF and the 6th nerve fascicle, and that’ll have a partial 6th nerve palsy. That makes it more complicated. Small lesions — a person comes in with just a gaze palsy. It’s gonna be a small lesion, because there’s all this other information in the brain stem. But small lesions in this area can cause an ipsilateral horizontal gaze palsy. Here’s the schematic from Clinical Neuroophthalmology. I’ve kind of cut it off. You can get the idea. Here he is in primary position. When he tries to look to the left, neither eye moves to the left. That’s a left gaze palsy. When he tries to look to the right, the left eye does not move. A striking adduction deficit. But the right eye does move, and if this were a video, you would see some adducting nystagmus. So this person has a left INO, they have a left gaze palsy, and we call that a one and a half syndrome. So the one is the gaze palsy. The half is the INO. A one and a half syndrome. And that again can be caused by a very small lesion that might affect both the PPRF, the horizontal gaze center, and the MLF, so you get the horizontal gaze palsy, you get the INO, it could be a lesion here, that affects the MLF and the 6th nerve nucleus. Remember that a 6th nerve nuclear lesion causes a horizontal gaze palsy because of the interneurons running from the PPRF through the nucleus. So small lesions can give you a one and a half. This says my internet connection is unstable. That’s not good. Here’s a patient with a video we’ll play. This is obviously an elderly woman. She’s got a little bit of abducting nystagmus, she has a mild adduction deficit. Here she is, trying to look to the left. So she’s got a complete left gaze palsy. And a left — partial left INO. This is my best video of a left one and a half. So, again, small lesion that affects both the MLF and either the PPRF or the 6th nerve nucleus. So one and a half. Okay. Here’s a young woman in her 20s. That came in with double vision. And you can see I’m doing a cross cover test. Just to highlight that she has got a little vertical misalignment of her eyes. You’ll notice… I’ll show you — I think my next slide is another video. But in primary position, her eyes are pretty stable. But she’s got a little right hypertropia. And that’s why she’s having the double vision. This did not fit any cranial nerve pattern. But when we had her look upward, watch what we see. We see conjugate — both eyes — have a little upbeat nystagmus. A little upbeat. So when we see that conjugate vertical nystagmus, this has got to be brain stem or cerebellum, and so she has a little vertical misalignment that doesn’t fit any cranial nerve pattern, and mild upbeat nystagmus, worse in upgaze. So something’s going on in the central nervous system. And we call this little vertical misalignment a skew deviation. So a skew deviation, in my opinion — it’s kind of a wastebasket term for a vertical misalignment of CNS, central nervous system origin, that doesn’t — that’s not a 3rd nerve palsy, not a 4th nerve palsy. It can be comitant, the same wherever you look, or it can be incomitant. You don’t see ophthalmoplegia with this, because it’s a supranuclear problem. So there’s no ophthalmoplegia. Just misalignment. In this young lady’s case, in the United States, the most common cause of this would be demyelinating disease, or MS. And her MRI indeed showed these typical plaques that we see with multiple sclerosis. So she had a skew deviation. A vertical misalignment of the eyes of central nervous system origin, that doesn’t fit a 3rd, doesn’t fit a 4th. Here’s a young fellow with an interesting story. He saw an ophthalmologist who called me and said — I’ve got this young guy. He’s a college student. And all he complains about is some blurry vision when he rides his mountain bike. You know how college students are. They’re not very cooperative. I wasn’t sure what he meant. What do you mean? He said he won’t really look up. And here he is, trying to look up. So his horizontal eye movements aren’t bad. Not great for maybe a 20-year-old. But there’s his horizontal movements to the right. To the left. Down gaze is okay. Maybe not completely full for a young, healthy person. But when he tries to look from down to up, he has an upgaze palsy. Neither eye moves up, so we call it a gaze palsy. Since they’re not moving up in his case, it’s an upgaze palsy. I want you to notice two other things. Number one, he’s got some lid retraction. Watch when he tries to — look at his eyelids for a moment here. His lids are open real wide. He’s got some lid retraction. And when he looks from down to up, his eyes have some funny sort of rapid… Movements that look sort of like nystagmus. And indeed, this is called convergence retraction nystagmus and the eyelid retraction you’re seeing, as an eponym, called Collier’s sign. This is not thyroid eye disease, which also has lid retraction. But this is something else. So I asked the doctor. He told me — you know how college students are. They’re not that cooperative. How about his pupils? He said… That’s funny. His pupils aren’t very cooperative either. And here are his pupils reacting to light. You can see almost no reaction to light. But watch in a moment. You’ll be looking at a near target. Here he goes right now. And he has nice constriction of the pupil, and when he looks in the distance, it quickly dilates. So it constricts to near. But the pupil does not move to light. We call this pupillary light near dissociation. So he’s got multiple findings of light near dissociation, lid retraction, upgaze palsy, and convergence retraction nystagmus. So hopefully most of you will know what that constellation of findings means. And here’s… Let’s see if you do. So this is our second polling slide. Does this represent Argyll Robertson pupil, Adie’s tonic pupil, a problem in the dorsal midbrain, or does this person have bilateral 3rd nerve palsy? I’ll give you about 15 seconds to vote, and we’ll see what the audience thinks about this. Five, four, three, two, one. Very good. Two thirds of you say dorsal midbrain syndrome, which is exactly correct. It’s true that Argyll Robertson pupils are a cause of pupillary light near dissociation, as is a tonic pupil. However, those are isolated pupillary problems. This is certainly not an isolated pupillary problem. A couple people said bilateral 3rds. Very unlikely that bilateral 3rds are gonna cause elevation deficits. You shouldn’t see dissociation with 3rd nerve palsy, and certainly not lid retraction. You should see ptosis. So the correct answer is dorsal midbrain. This has another eponym. You can see Parinaud’s dorsal midbrain syndrome. Here’s the pons. Here’s this tumor, which turned out to be a germinoma, sitting right on his midbrain, causing a dorsal midbrain syndrome. Here’s a schematic showing the same view. What lives in the dorsal midbrain are the rostral interstitial nucleus, which form the vertical gaze centers. You can see not only upgaze palsy, but a complete vertical gaze palsy. But that’s where the lesion should be. And in his case, that’s where it was. He actually did very well with treatment and is still doing well to this day. That video is probably at least 15 years old. So we’re gonna switch a little bit here. This is an interesting woman who’s 50. This is maybe a little more esoteric. And so what you’re seeing here are her attempts at saccadic eye movements. You can’t see me, but I’m asking her to look at my nose and at my finger. Horizontally, she does pretty well. Here she is. There’s a horizontal saccade to my finger, and back to my nose. But what you’re seeing now is her attempts at saccading up and down. That’s up, and somewhere in here is down. She just can’t saccade vertically. But she can saccade horizontally. So she has a problem that’s affecting it. Otherwise, she really couldn’t have eye symptoms. In fact, she was sent to me with a specific question. Do I see evidence of a certain condition? Her problem and the reason she was sent to me is she’s having some problems with her gait. She feels a little bit offbalance. And she’s having some problems with her memory. She was a school teacher. She said… My memory is not terrible, but once in a while, I have trouble remembering how to tie my shoelaces. So here she is, pursuing my finger. I’m moving my finger slowly. As I keep following my finger, moving it up and moving it down… And you’ll see that her pursuit eye movements are very good. Look at how well she pursues. So this is a condition that affects saccades before it affects pursuit. Pursuit eye movements. Here she is again, pursuing upward and pursuing downward normally. So I don’t think I’m gonna quiz you on this one. This one is a tough one, I think. Anybody who knows the answer can shout it out, although I won’t hear you. So she’s got what’s called progressive supranuclear palsy. It’s got an eponym, which I don’t think anybody remembers. Smith-Olszewski-Steele syndrome. This is a midbrain degenerative disease. Unfortunately it’s often fatal, and the average is six years. People die because they develop problems not just with walking and balance, but with swallowing, and they often die of aspiration pneumonia. The vertical saccades are affected first, but it can progress to complete ophthalmoplegia. These patients have not only blepharospasm, but a combination of blepharospasm and apraxia of eyelid opening. Your eyes can close, and they just won’t open them. You can imagine if someone has blepharospasm, where they’re constantly blinking and shutting their eyes, and they won’t open when they relax, that’s not a good problem to have. So this is not common, but I do see it. This is occasionally misdiagnosed early on as Parkinson’s disease. So sometimes patients are sent to me with doctors asking — does this look like Parkinson’s disease or PSP? So this is a polling question. I don’t know that we’ll show the poll yet. Let’s watch the eye movements. This is a fellow who has had double vision. He’s had double vision for a couple of months. You can see his eye movements here. You can see from his eye movements that he is esotropic. And his vertical eye movements don’t look so bad. His horizontal eye movements are not real normal, necessarily. But I also will mention, for those of you who were at my part I of the ocular motility, never forget to look at what I call the fellow travelers. The fellow travelers. And for those of you who were at the lecture, maybe that will clue you into the diagnosis. For those of you who weren’t, maybe you’ll get it anyway. But we’ll talk about it anyway, after we vote. So cast your vote. What does this represent? Myasthenia? 6th nerve palsy? Bilateral 6th nerve palsy? Or is this Graves’ or thyroid eye disease? Let’s see what you said. Very good. The majority of you have got this correct. The person certainly does have bilateral abduction deficits. So the second most common answer was bilateral 6th nerve palsies. There are definitely bilateral 6th nerve palsies. I’m not sure if you’re seeing that, or… So he definitely has bilateral abduction deficits. This could be myasthenia, because myasthenia can mimic anything. It could be myasthenia. It’s not a unilateral 6th nerve palsy. It could be bilateral 6th nerve palsy. But there’s a very important fellow traveler. By fellow traveler, I mean whenever you see someone with double vision, with ophthalmoplegia, you want to look closely at two other things. Number one, the pupils, and number two, the eyelids. Look right there. He’s got marked bilateral eyelid retraction. And other than Parinaud’s — and this is not that, because he has good vertical eye movements — by far more common than Parinaud’s is thyroid eye disease. So look at that lag. He’s got not only lid retraction, but lid lag. He’s got thyroid eye disease. You don’t even have to look at his eye movements. Just look at that picture. I don’t care what his eye movements are. Nothing else causes lid retraction and lid lag. You don’t need to see his eye movements to make the correct diagnosis. And thyroid eye disease can look all sorts of ways. It can look like our photo in the upper left. This is the sort of active, angry-looking painful thyroid eye disease. Very acute. And it doesn’t look real comfortable. Or it could be white and quiet looking. In our upper right, this marked bilateral upper and lower lid retraction. And in her case, she did have exophthalmos. It can be even unilateral. In the bottom frame, we see upper and lower lid retraction and exophthalmos. It’s a condition like myasthenia. Sometimes even myasthenia can look unilateral as well. It can just look that way. I don’t know why. And Graves orbitopathy — I tend to prefer thyroid eye disease. More common in women than men, but men get it. 80% of patients present with the eye findings during or after being hyperthyroid. About 10% never get hyperthyroid. They are hypothyroid. And 10% are euthyroid. So I talk to people about thyroid blood problems and thyroid eye problems. You can fix your thyroid blood problem and it may have no effect on your thyroid eye problem. How do you treat the thyroid blood problem? Usually we give you medicine to get your thyroid not to work as much. Sometimes we remove your thyroid, we kill your thyroid with radiation, when we don’t want to do any of those things to your eyes. And so we wait and we watch. Sometimes we will use pulse intravenous steroids once a week. For 6 to 12 weeks. I would favor that in our patient we saw in the previous slide with the very active, angry-looking thyroid eye disease. Sometimes patients come and say — we ruled the thyroid problem out with the blood tests. I say, no. About 10% of patients are euthyroid. They do not have a thyroid blood problem. Just a thyroid eye problem. The pathology, which I’m not gonna dwell on, is a lymphocytic and plasma cell infiltration. So you end up with edema, proliferation of orbital fibroblasts, increased synthesis of glycosaminoglycans. Here’s a picture. You can see without even looking at the eye movements, she’s got lid retraction. And if you look at the eye movements, you’ll notice she has striking bilateral abduction deficits, and if you look at the top center or any of the top frames, you’ll see she really doesn’t have great elevation. Her right eye is sort of stuck slightly elevated, compared to her left, but she has bilateral abduction and bilateral elevation deficits, most consistent with thyroid eye disease. Plus you throw in the lid retraction and there you’ve got the diagnosis. I ask my residents when I show them this — how do you think she was being treated at this point? The answer was she was patching her right eye. She only put makeup on her left eye. She didn’t need to put it on her right eye. It was patched. And scans — for reasons which are unclear, it’s usually the inferior rectus muscle involved first, medial rectus second, superior rectus third, lateral rectus fourth. So if you have someone you think has thyroid eye and all they’ve got is a big lateral rectus, probably think again. Here’s an enlargement of the muscles, axial view showing the large medial recti with the so-called tendon-sparing, and you can see in this bottom photo how the patients can end up with a compressive optic neuropathy. Your orbit is shaped like an ice cream cone, and at the back, it gets pretty narrow. If you have big muscles like this, you can imagine that the optic nerve — since the bone isn’t going anywhere, the optic nerve loses. And you can develop a compressive optic neuropathy. Here is a patient who might initially look like thyroid. You can say — there’s that active-looking chemosis, maybe a little lid retraction over here. Although this eye looks — and according to the patient, feels — completely normal. But the history is somewhat helpful here. A week prior to these photos, the patient says — I was completely normal. No problems whatsoever. So thyroid eye disease usually doesn’t occur acutely like that. Over a week, the eye got red. It’s rather painful. And of course this patient has double vision. You can see the eye is not abducting well. It is moving otherwise okay. But there’s a lot of chemosis, swelling, a little erythema around the orbit. And the differential diagnosis for this would include orbital cellulitis. So clearly you would want a CT scan, at minimum, to look at the sinuses, to make sure that there’s not sinusitis, sinus opacification. If so, clearly you treat this patient with antibiotics. And probably steroids, but if there’s no sinusitis and your suspicion of orbital cellulitis is low, the most common second thing would be idiopathic orbital inflammation. Or orbital pseudotumor. This is the CAT scan of the patient — not that same patient, but of a different patient — who came in with fairly acute onset of double vision, swelling in the eye socket, and they just had this big lateral rectus muscle on the left. Here you can see the small normal sized lateral rectus on the right. This patient had a subset of orbital pseudotumor, called orbital myositis. Just affecting one muscle in this case. Idiopathic orbital inflammation or orbital pseudotumor can affect the whole orbit, one of the muscles, multiple muscles, usually it’s fairly acute or subacute in onset, often very painful, usually but not always — usually unilateral. And it’s really characterized by a typically rapid response to corticosteroid. So we put these people on a moderate dose of corticosteroids. I use prednisone, 40 to 60 milligrams. And it’s amazing. Within a couple of days, usually the patient is saying — wow, this is a miracle drug. In fact, I see them usually in a couple of days to make sure they’re saying that. If they’re not, I worry about my original diagnosis. And typically these patients of course have no other symptoms. It’s typically unilateral, sometimes bilateral, but there’s no other systemic abnormalities going on. So orbital pseudotumor or idiopathic orbital inflammation. All right. We’re gonna switch tacks a little bit now. This is a young lady who was sent to me with abnormal eye movements. She is actually asymptomatic. She went in for glasses, and the doctor said — gee, your eyes don’t move well. She said — it doesn’t bother me. I didn’t really notice. And the referring diagnosis was bilateral internuclear ophthalmoplegia. Bilateral INO. The most striking thing about her eye movements are the bilateral adduction deficits. So here she is, looking up. So notice the adduction deficits. But I think you’ll agree that if you look at her eye movements in general, she’s 19 years old, she does not have normal elevation of either eye. That’s not normal for a 19-year-old. And she doesn’t have normal abduction or depression for a 19-year-old. So she in fact has more generalized ophthalmoplegia. The adduction is the most striking, but she really has bilateral — relatively symmetric — ophthalmoplegia, with no double vision, and she has some ptosis. Right? Not a lot, but for a 19-year-old, her eyelids are a little droopy, and she did produce some photographs from when she was a kid when her eyelids did not look that way. So she’s got bilateral ophthalmoplegia with no double vision and bilateral ptosis. This is fairly characteristic of this condition, called chronic progressive external ophthalmoplegia, or CPEO. This is a mitochondrial myopathy. It could be coded by a mitochondrial DNA, or it could be coded by somatic DNA. Usually when patients present early on, what they complain of is ptosis. For whatever reason, they don’t seem to develop double vision. Sometimes if you ask them — hey, do you ever get double vision? Well, maybe, but nothing that really bothers me. So they usually don’t come in complaining of double vision. They come in complaining of… My eyelids are drooping. Please fix them. Don’t forget to check the orbicularis weakness. That’s one of the fellow travelers. Usually not as profound as myasthenia gravis. You can get orbicularis weakness. The ophthalmoplegia is usually fairly symmetric. I would be hesitant to make this diagnosis in someone who does not have symmetric ophthalmoplegia. Remember there’s also a subset of these patients who have something called the Kearns-Sayre variant. These patients can have a retinitis pigmentosa funduscopic look, but they can get various degrees of heart block, cardiac arrhythmia. And need pacemakers. If they don’t have a pacemaker, they can die of complete heart block. It doesn’t happen overnight. But it can happen. So if you have a patient who you think has CPEO, you need to get an electrocardiogram to look at their rhythm. I saw a patient who was actually diagnosed with CPEO, and I asked about whether the neuroophthalmologist had ordered an EKG, and they said no. But I did have an EKG, because I had a cardiac procedure. And I’ve got a bundle block. I said you need to see a cardiologist and talk about a pacemaker, to prevent you have having serious cardiac problems. They may also have increased cerebrospinal fluid protein, and ataxia. Classically, it’s a male, not a female. Though it can occur in females. She in fact did not have Kearns-Sayre. We ordered an EKG. That was the only thing we ordered. And we sent her on her way. She did not want eye surgery. There was nothing we could do about the eye problem. This was a patient with ptosis, and she had ptosis surgery, and presented again in her late 30s with recurrent ptosis, and had a little more eyelid surgery. And came in, in her mid-50s, and wanted more eyelid surgery. The surgeon said — you have droopy lids, but your eyes don’t move very well at all. She has very symmetric generalized ophthalmoplegia, bilateral ptosis, two previous eyelid surgeries, over the last few decades. This clearly looks like CPEO. What’s in the differential? You need to think about myasthenia gravis, in somebody with ptosis. But this is not myasthenia gravis. She’s never had double vision. She has noticed that she has to turn her head to the side more. But this is a very gradual, chronic progressive sort of a problem. And I said gee, you know, this is something that can run in families. Do you have any kids? Three daughters. Do any of them have your sort of appearance? She said one of them looks kind of like I look. Do you have any photographs? I don’t have any photographs, but better, she’s out in the waiting room. Here’s her daughter. And you can see, she’s got CPEO. I’ve somehow lost photographs of her eye movements, which weren’t as bad as her mom’s. But she had mild generalized ophthalmoplegia, and obvious bilateral ptosis. A little worse on the left than the right. The other thing that they both have is what’s called the masked facies. Kind of this expressionless face. They both had that. This is chronic progressive external ophthalmoplegia. All right. Another topic. Here’s a woman, she’s 75, pretty healthy. In fact, is taking no prescription medicines. And says — I never get sick! although about a month ago, she had a couple days of some sort of… She thinks a viral stomach kind of a thing. Some diarrhea. That went away on its own with no treatment over a couple of days. But then she developed double vision. This is how she looked. I was seeing her — she was in the hospital. Not my hospital. A different hospital. For a week. She had multiple, multiple tests, all of which were negative. One of them was still pending, and they sent her to me on her way home from the hospital. She stopped in my office. This is her upgaze, left gaze, right gaze, and downgaze. That’s it. So she has complete bilateral ophthalmoplegia. She had a small esotropia. That’s why she had the double vision. And a little bit of ptosis, but not bad. So complete bilateral ophthalmoplegia. What sorts of things might cause this? You have to think about myasthenia. I hope I don’t have that question slide here. You have to think about myasthenia, because that can mimic anything that causes ophthalmoplegia or ptosis. In the hospital, she already had a blood test, already had a Tensilon test, and an MRI. All of that was normal. The question is: What is going on? So one test she did have drawn, to their credit, that hadn’t finished, was the anti-GQ1b antibody test. This is the Miller-Fisher variant of Guillain-Barre. So people have problems with their tendon reflexes, if you test them. This is a postinfection problem, often after infection with campylobacter. And it causes you to make antibodies, these anti-GQ1b antibodies, that are specific for internodal regions for ocular cranial nerves. So you see ophthalmoplegia. Sometimes it can affect pupils. I’ve seen reports of pupil involvement, usually bilateral and symmetric. Typically this condition gets better. She was treated with intravenous immunoglobulin for a couple of days, and she came back six weeks later, because I told her she would probably be getting better. When she came back, she said… You lied to me! Because I am no better. Let’s look at her eye movements. And you can see that… Clearly her eye movements are much better. So why was she saying I lied to her? What’s the problem? The problem is that, although her eye movements are a lot better, they’re not completely normal, and she still has double vision. So remember, for a patient, double vision is either there or it isn’t. For her, she said — I’m no better. Fortunately, her daughter was with her and said mom, your eyes are moving much better. I guarantee it. I showed her the video. She said… All right, maybe you’re right. She came back six weeks later, with no double vision and normal eye movements. So the anti-GQ1b antibody syndrome. All right. So this is another fellow, and I think eventually there’ll be a polling slide. So I’ll ask you to vote on this. So think about it as we’re talking about him. He’s 56. Has double vision just for the last week. He’s treated for hypertension and asthma. His acuity is normal, 20/20 or 6/6. His pupils are normal as well. His problem with the double vision is primarily when he’s reading. When he looks downward, he notices the vertical binocular double vision. And a very mild deficit in depression of the right eye. So a mild problem on the right with depression. Let’s look at the video, not so much of his eye movements, but of his fellow travelers. I’m gonna let you just look at this video here. In a moment, we’ll open the polling. And I’m not gonna give you any hints, I don’t think, while we’re watching the video. All right. Let’s open the polling. And see what you guys think. I’m gonna try to get this out of the way here. So is this myasthenia? Is this the 3rd nerve palsy? Internuclear ophthalmoplegia? Or thyroid eye disease? We’ll give you another 10 seconds or so. Five, four, three, two, one. Call it. All right. Very good. So the majority of you got this right. This is indeed myasthenia. A small number said 3rd nerve palsy. A small number said INO. Shame on you. There’s nothing about this that looks like an INO. I’m not even showing you horizontal eye movements. You can get rid of the poll there. Graves’ disease causes eyelid retraction. This guy has a little drooping of both eyelids, more on the left than the right. So I’m pretty quickly gonna eliminate Graves. The other reason to eliminate Graves is — remember, the most common muscle involved in Graves’ disease is the inferior rectus. And I didn’t mention — maybe I should have — when those muscles get enlarged, they still work okay. They don’t relax okay. So the most common pattern of ocular misalignment in Graves’ disease is actually vertical misalignment when you look up. Not when you look down. His problem is when you look down. So that would be not typical for Graves, plus he has ptosis, not lid retraction. 3rd nerve palsy — well, 3rd nerve palsy could cause a droopy lid, but this guy, his problem, as I said early on, his double vision is a problem with his right eye not moving all the way down. But once you look at the video, you notice — gee. He’s got left ptosis, more than right. This is a bilateral process. So you’re gonna probably not be thinking about cranial nerve palsies, as most likely. It’s not common to have bilateral cranial nerve palsies. So you’re gonna have something systemic. And the final thing I’m trying to show you in the video is the upper left eyelid. Watch what happens. It moves up and there’s a little twitch. This is called Cogan’s lid twitch sign. This is one version of it. I’m gonna show you another version in a minute. So this is Cogan’s lid twitch, in the setting of right depression — this has got to be myasthenia. Got to be. So as far as symptoms go, we think about variability and fatigability. Those are the hallmarks of myasthenia. It doesn’t mean it has to be variable and fatigable. But you have to ask about it. You can have variable and fatigable ptosis, double vision, or even lagophthalmos, the inability to even close your eyes, because of the weakness of the orbicularis muscle. Sometimes patients don’t have double vision. If there’s a mild misalignment. They may just call it blurry. But if you ask them does it get better if you cover each eye, they say yes. It’s something binocular. So if it’s a very mild misalignment, they may not say double. Also remember that non-myasthenic double vision and ptosis may get worse at the end of the day. If you have levator dehiscence and you’re using your frontalis muscles all day to keep your eyelids open, at the end of the day they may be weakening, and most people with ptosis for any reason will say yeah, it’s worse at the end of the day. My question to increase or decrease my level of suspicion is — do you ever have to hold your eyes open at the end of the day to see? If they say yes, that sounds like myasthenia. If they say — yeah, my lid closes at the end of the day, it’s got to be myasthenia. And same with double vision. If they have a mild misalignment of the eye, and they can use their fusional abilities to overcome it, it may get worse at the end of the day. So just because it sounds fatigable doesn’t mean it is myasthenia. What about the signs of myasthenia? Variable ptosis. You can attempt to fatigue it. I’m gonna show you the video. Cogan’s lid twitch, and don’t forget to check for orbicularis weakness. Here’s the same patient. Look at the left upper eyelid. See it go up and then down. There’s a little twitch. A little twitch. Cogan’s lid twitch. I think I’ve got one more video. Here’s a lady with obvious ptosis. This takes a second or two. I need to edit this. But you can look at her eye movements, which don’t look terrible. Her lid is — see, it’s twitching just a little bit there. A better example. There goes! keep watching. There it is. A little twitch of that lid. A little more. There it goes again. So she also has Cogan’s lid twitch. There it was. There it goes. Cogan’s lid twitch sign. Look for it. Here’s a fellow — ptosis on the right and double vision. This is realtime, unedited. He’s looking at my finger up above his head. There goes that lid. Fatigable right ptosis. Virtually nothing is gonna look this way. You see it? He’s got myasthenia gravis. And here we’re checking orbicularis strength. This woman is trying to keep her eyes closed as tightly as she can, and you can see when I let go of either lid, it just kind of flops back into place. There is no tone in the orbicularis. This has got to be myasthenia. So look for variable ptosis. Attempt to fatigue it. Look for the lid twitch. Check orbicularis strength. How about the motility signs? Remember, as I’ve already said, it can mimic any pattern. I’ve seen it mimic unilateral INOs, bilateral INOS, 4th nerve palsies, 6th nerve palsies. The measurements may vary, and they may have misalignment even with full-looking eye movements. So here’s the woman with the orbicularis movements. She was sent to me with bilateral INOs. You can see a striking abduction deficit. I’m making her look in right gaze to see if I can fatigue her movements. It’s not a great example of fatigue. But here’s her left adduction deficit. Watch when she looks to the right, which she will do in a moment. So again, no adduction. That’s why the neurologist thought this was a bilateral INO. She already had MRI, and he said — gee, she’s got bilateral INO. Her MRI is normal. Watch when she tries to look downward. I’m gonna hold her lids open. This is downgaze. That’s it. So what the neurologist didn’t appreciate was her basic complete lack of depression of each eye. So this is not an isolated bilateral adduction deficit. This is a bilateral adduction deficit and bilateral depression deficit, and when you check her orbicularis strength, there is no tone. This has got to be myasthenia. And here’s a patient with fatigable ophthalmoplegia. So look at his right eye. We’ll let the video loop. Look at how much sclera you’ll see, as time goes by. This is unedited. And the video will loop. His eye is almost back into primary position at the end of the video. Here we are at the beginning of the video. Just in that much time, watch the eye gradually drift back towards center. The other eye is not moving. So this is fatigable ophthalmoplegia. So it can mimic anything. Measurements may vary. Movements may appear full. Can be unilateral or bilateral. What about testing? Well, there’s something called the sleep or rest test, described many years ago now by Jeff Odell, a friend of mine, where you would have the patient close their eyes for 30 minutes, and measure the degree of ptosis before, and after 30 minutes, you go into the room, say open your eyes, look straight ahead, and you look to see an improvement in the ptosis. Here’s an example of the rest test. So the fellow before the rest and after the rest. You can see the marked improvement in the ptosis, after the rest test. The other test that we tend to do — because who’s got 30 minutes? I don’t. Is the ice test. This is a paper we published back in I think 2000, where we looked at 30 patients with ptosis of known causes, such as levator dehiscence, 3rd nerve palsy, Horner syndrome, and we had 20 patients with myasthenia, with positive blood testing and/or positive Tensilon testing. So 20 patients with ptosis. We applied an eye pack for 20 minutes and found that none of the 30 patients with non-myasthenic ptosis had improvement, whereas 16 of the 20 with myasthenic ptosis had improvement of more than 1 millimeter. Of those, four had complete ptosis of one of the lids. Cooling that eyelid did not help. Cooling the eyelid did not help. So of the 17 patients with incomplete ptosis, 16 of 17 had improvement of greater than 1 millimeter. So very specific and sensitive. If the ptosis is complete, all bets are off with the ice test. But what else causes complete ptosis? 3rd nerve palsy — pretty much it. So usually you’re not gonna be fooled. Here’s a fellow with ptosis on the right, obviously. You’ll quickly notice he’s got a left abduction deficit. So if you see a person — bilateral findings, ptosis on one side, ophthalmoplegia on one or both sides, you’ve got to be thinking myasthenia. I’m gonna show you his ice test in just a moment. Let’s look at his degree of ptosis. At the end of the video, we’ll look at his ptosis again. Obvious right ptosis, right? Let’s look at his ice test. Here we are, at the end of two minutes. Boom! so… And it quickly goes back, because your eyelid warms up pretty darn fast. How does that work? Don’t know for sure. We think we’re cooling off the chemical reaction of the acetylcholinesterase. You cool it off — it’s kind of like Tensilon. Doesn’t act the same way, but you’re inhibiting the acetylcholinesterase reaction. So greater than 1 millimeter improvement, positive test. You can do Tensilon or edrophonium testing. I haven’t done a Tensilon test in at least a decade. In kids, you can use a neostigmine or Prostigmin. The only reason is in a kid who’s not that cooperative. The Tensilon test doesn’t last that long. This guy has double vision, abduction deficit, a little ptosis. An injection of Tensilon. A minute goes by. His lids pop open, looking at the chart at the end of the room, his double vision goes away. But within a minute or so, the effects of the Tensilon go away, and it comes right back. So it’s a diagnostic, not a therapeutic test. You can get blood tests. The antiacetylcholine receptor antibodies. I typically check the binding antibodies. There are blocking and modulating as well. I don’t find those helpful. I usually just check the acetylcholine receptor antibodies, binding. The problem is if it’s just ocular, if the patient has no symptoms of systemic myasthenia, the blood tests are only positive 50% or 60% of the time. So I tell the patient who has just ocular symptoms — listen, we’re gonna get a blood test. If it’s positive, it’s very helpful. If it’s positive, you’ve got myasthenia. There’s almost no such thing as a false positive. On the other hand, if it’s negative, it doesn’t mean anything. There is no test that rules out myasthenia gravis. If there are systemic symptoms, it’s much more likely to be positive. And you can could single fiber electromyography. Some places in the United States will do orbicularis EMG, even extraocular muscle EMG. Not many do that. So in summary for myasthenia, consider myasthenia in anybody with double vision or ptosis. At least think about myasthenia, and look for the signs we’ve talked about. Check for the variable, fatigable ptosis, Cogan’s lid twitch, orbicularis weakness. Don’t forget that stuff. Remember that myasthenia can mimic any pattern of ocular misalignment. Hence you need to consider it in anybody with double vision. Rest and/or ice testing can be helpful, and again, just to make my point, consider myasthenia in everybody with double vision or droopy lids. So… In summary, for ocular motility part II, look for those patterns we talked about. Brain stem patterns, INOs, one and a halfs, gaze palsies. Don’t forget to check the fellow travelers. Look for orbital signs in all patients with ocular motility deficits. Exophthalmos, chemosis, et cetera. Remember that myasthenia can mimic any motility problem. Check for fatigability, orbicularis strength, and the other signs we talked about. So that’s the end of motility part II. There are some questions and people can type in questions. Sorry, I forgot to say that you can type in questions in the chat area. I don’t know if I have to… I don’t see any of the questions at the moment. I’m not sure if I have to stop sharing in order to see those? Stop sharing my screen and see what happens. Ah-ha. That may be it. Okay. And let me check on… Questions and answers. Okay. And if anyone has any questions they want to type in, feel free to type them in, as we’re trying to answer the questions. So let’s see. I’ll start with the — why was she patching her right eye? I think this has to do with the patient with the thyroid eye disease. So in terms of patching, and double vision, I usually — the short run treatment for double vision, I mean, obviously, if you can cure the underlying problem, oftentimes we can’t cure it quickly… The short-term treatment is occlusion. So it could be a patch. I like to use just scotch tape. Opaque tape on the lens, if the patient is wearing glasses. That works great. I don’t care which eye they cover. As long as they only cover one of them at a time, and don’t switch the patch. So as long as it’s not a kid, who could be in the amblyopic age range, I don’t like switching the patch. It makes the patient offbalance every time they switch the patch. I don’t care which eye they pick. Whatever eye they feel comfortable with is the eye that we patch. Let’s see. A child aged 6 years old with horizontal gaze palsy, vision is subnormal. Best corrected vision is 6/18. Orthotropic in primary. Improved with patching? I guess one question is why does she have horizontal gaze palsy? If you truly mean neither eye moves to one side, the question is: Why is that? Does she have a Duane’s syndrome or an abduction deficit? Clearly that’s a little bit of a different story. I think that if her best corrected vision looks symmetric, and she… Sorry, this thing keeps jumping on me. She has poor stereo acuity… But she’s orthotropic in primary. Will she be improved with patching? I’m not sure why she’s amblyopic. You would think if she has an ocular motility problem, she would have some sort of strabismic amblyopia. I assume your question means she’s 6/18 OU, which really makes no sense to me at all. If she’s 6/18 OU, I wouldn’t know which eye to patch, and if she’s orthotropic, I don’t think patching would help. I would probably feel more comfortable asking this to one of our pediatric ophthalmologists. I think this might be a good case to post on the Cybersight consult thing. And give them all the information, and it would go to one of our pediatric ophthalmologists. Probably not me. But that doesn’t add up well for me. What are the fellow travelers? So the fellow travelers are the things that you really want to think about when someone has a motility problem. What things do you want to think about? You want to think — what nerves and other findings might you see? So in Graves’ disease, myasthenia, 3rd nerve palsy, clearly the eyelids are very important. So one of the fellow travelers is eyelids. Is there ptosis? Is there lid retraction? Is there fatigable ptosis? Those sorts of things. Is there… What about the pupils? So in 3rd nerve palsy, we’re very interested with the pupils, in Parinaud’s, we’re interested in the pupil. You want to look for pupil anisocoria, pupillary dissociation, how the pupils are reacting. So those are fellow travelers. But also you’re gonna look for orbital signs. Is there exophthalmos? Is there any chemosis? All right. Who treats MS? Us or refer to neuro? I always refer to neuro. I will treat acute double vision or optic neuritis with typically with high doses of intravenous corticosteroids. But I don’t personally use the multiple sclerosis medicines. Anybody with MS, in my opinion, needs a neurologist to go over them systemically, and I let the neurologist recommend the form of chronic systemic treatment. I will treat with steroids acutely, but I always have them see a neurologist. When can I plan for strabismus surgery in patients with myasthenia gravis? Almost never. I’m saying that sort of jokingly. As you know, myasthenia, and as we just talked about, one of the hallmarks is variability. So the times that I would consider strabismus surgery in someone who I have followed for probably… At least a year with no significant change, in their alignment, and even then the strabismus surgeon, if they’re willing to do the surgery, is gonna have to tell the patient — listen, we could do the surgery tomorrow and you could have a great result, and in two weeks, if your myasthenia acts up, you could be back with double vision. So the patient has to be willing to take that risk, and so does the surgeon. In the case of orbital myositis, when do you stop the corticosteroids? So I treat the patient with 40 to 60 milligrams of prednisone for about a month. I want them back to normal before I start to taper the prednisone. It’s gonna be at least a few weeks. Back to normal. The mistake I often see is the person gets better in a week, the ophthalmologist says great, taper the steroids over another week, and the problem comes right back, and so I usually give them a week or two longer than they’re normal. And taper them over the next couple of months, on a weekly basis, and hope it doesn’t come back. If it comes back, then I feel I’ve tapered too quickly. I bump them up and taper them more slowly. Will myasthenia gravis burn out after a certain period? Myasthenia gravis can go into — quote, “remission”, end quote. It can go into remission for forever, a month, a year. I showed you a fellow with fatigable ptosis. The interesting backstory to that is that two years previously he presented to me with double vision. He had what looked like a 4th nerve palsy. At that time, I thought this looks like a microvascular 4th nerve palsy. He was 52, had high blood pressure. I might have thought about myasthenia. But I didn’t think he had myasthenia. I said it’s gonna get better. Come back in 6 weeks. Came back, better. Two years later, he called me. My eyelid is drooping too. He came in with fatigable ptosis. I was wrong two years previously. He went into remission for two years and it came back. So it could go into remission for forever or never. So I don’t use the term burnout. I use the term remission. Can you clarify the time of the Tensilon test? So the way the test is done is you intravenously inject the edrophonium. You usually have 10 milligrams in your syringe. You have a tube — a vial of atropine, liquid atropine, next to you, to inject into the patient, if his heart stops. Which happened to me twice. Which is why I don’t do a lot of Tensilon tests. So you give 2 milligrams of the Tensilon. That is usually enough to give a positive response. So if you give 2 milligrams, you wait. Usually it’s in the 30 to 90 second range. And if it’s gonna have an effect, it has an effect. So you get a positive response, the ptosis goes away, don’t give the remaining 8 milligrams. The test is over. If it doesn’t go away, I give the other 8 milligrams. And then if nothing happens, it’s a negative test. But usually you see a response within 30 to 90 seconds. And it goes away within a couple of minutes. Who treats myasthenia? That’s also a good question. So I used to let the neurologist treat myasthenia. The problem is that I see a lot of patients with receptor negative ocular myasthenia. So that means they’ve had their acetylcholine receptor antibodies, they’re normal, and I used to send those patients to the neurologist and said — hey, I’m sure this is myasthenia. And I found out the neurologists were telling the patients I don’t think you’ve got myasthenia. Your blood tests are normal. You don’t have anything else going on. And they weren’t treating them! so now I treat patients with receptor negative myasthenia myself. And as long as they don’t develop systemic symptoms, I don’t have them see a neurologist. On the other hand, if they have positive blood tests, they’re also more likely to develop generalized myasthenia, and then I always make them go see a neurologist to go over the rest of them, so they have a neurologist, in case they have a problem, and I let the neurologist treat. How long do you advise for patching in the case of Graves double vision? So I tell them — this condition usually runs a course over 6 to 24 months, and then it burns out. So I do use the term burn out for Graves. And then is stabilizes. I follow them every couple of months. They patch for that time. Once I’ve decided they’re stable, which to me means no change in their misalignment for four months, then I either treat them with prism, if there’s mild misalignment, or refer them for strabismus surgery. Can we have your email? Yes. My email is very simple. It is… My last name, Golnik, followed by my first name, Karl, with no punctuation in between, at Gmail.com. So last name-first name@Gmail.com. How do you diagnose external ophthalmoplegia? I assume you mean chronic progressive external ophthalmoplegia, or CPEO. Personally, I think it’s a clinical diagnosis. There are genetic blood tests that can be considered. They don’t capture everybody. In the United States, those genetic blood tests cost probably in the order of $1,000 US, which usually in the United States is not paid for by insurance. So number one, there’s no treatment for chronic progressive external ophthalmoplegia. Number two, if the test result comes back normal, there’s a little asterisk next to the result, that says — by the way, this doesn’t capture everybody with the condition. So my patients typically don’t want to spend $1,000 US for a blood test that doesn’t lead to treatment. And doesn’t always give you an answer. Who sends you more patients? Physicians or ophthalmologists? I would say probably most common are ophthalmologists. But very quickly followed by neurologists, and in the United States, optometrists can practice independently, and they see a lot of primary eyecare. So I probably see… I will bet you… Two thirds of my referrals are from ophthalmologists and optometrists, and one third are from neurologists, neurosurgeons, and some primary care doctors, but probably the majority of that other group would be neurologists. Question. What are the brain stem patterns commonly seen? So I think that the ones that we talked about at the beginning of this — so the ones — I tried to cover the most common. There are lots of potential brain stem syndromes. But certainly by far the most common one I see is internuclear ophthalmoplegia, INO, either unilateral or bilateral. The second most common is probably a skew deviation. I don’t see lots of gaze palsies. But those are probably the most common. I’m a nurse and I have a 34-year-old male who presents with difficulty seeing lateral vision of the left eye. So I assume that means there’s a left temporal visual field defect. The vision… Central vision is good in each eye. Eye movements cannot move up and out movement of the left eye. No double vision, no ptosis. No injury. What could this be? So… Good central vision. And so it’s unclear to me whether the problem is strictly a motility problem, in other words, the eye just doesn’t move up and out. Or is there also a peripheral vision problem? I’m going to assume it’s just an eye movement problem. So this would be a pattern that doesn’t really fit a cranial nerve problem. Certainly, you know, the 6th nerve would be the nerve that would give you an abduction deficit. The abduction deficit… Should be present, though, whether you’re looking up or down. So if you’re saying that the eye does move down and out okay, that’s not a 6th nerve palsy. So it doesn’t really fit a specific pattern. So in that scenario, I would be interested in things like myasthenia. I would be interested in a CAT scan of the orbits, probably, to look at the eye muscles. Could this be a large inferior rectus? But that’s probably the best I can do, without more information, or seeing the patient. Is it safe to perform a Tensilon test in the office? So for many years, I did Tensilon tests right in the office. As I mentioned, I had two patients who passed out because of low heart rate. And who needed the atropine. After the second one, I started doing them… We have a same day surgery office in my building. We have 7 ORs in my eye Institute. So I started doing them in the downstairs, under more monitoring. Because I didn’t want someone dying in my office. The answer is, if you’re gonna do a Tensilon test, I would recommend doing it with at least some monitoring available. I think you can be in problem if you have a problem, and a known risk is stopping your heart, like I said, I haven’t done a Tensilon test in at least ten years. Because of the other testing available. Do I need to search for thymoma for all ages in myasthenia? The answer is yes. I’m hoping at some point the answer will be no. Ask me the last time I’ve found a thymoma. I’ve never found one in ocular myasthenia. Does myasthenia involve the pupil? After rest, the pupils look dilated. Good pickup. We did dilate the patients while we did the rest test. You could argue that maybe the dilating drops improved the ptosis. But within 30 minutes after the photo was taken, the eyelid went back to the droopy lid. So it wasn’t just the dilating drops that caused the ptosis to improve. But we did dilate the patient because I didn’t want to wait 30 minutes and then dilate the patient. Waiting 30 minutes was hard enough. The ice pack test was done for 2 minutes. Believe me, it gets cold. I have patients complain — this is cold! the alternative is a medicine that might stop your heart! that shuts them up pretty fast. Use of clinical activity score for Graves’ disease… I know there’s a clinical activity score. If you find it helpful, use it. I don’t find it helpful. I don’t use it. But if you’re writing papers on Graves, then you probably wanna do it. If it helps you yourself, use it. I personally don’t. What is the role of botulinum toxin in the case of Graves or myasthenia? Hm. Um… I know of no role for botulinum toxin in myasthenia, and I would avoid it. I think the role in Graves I guess could be… When you have these tight muscles, once they’re tight for a while, they can scar that way. I think that some of our strabismus surgeons might use botulinum intraoperatively, to try to loosen them up a bit. But I don’t know. And I don’t do strabismus surgery myself. But I think some of our surgeons sometimes will use botulinum toxin in Graves. Although I am not positive about that. Again, the features of anti-GQ1b, that should be, not 21. 1b. So the features are… This again is the variant of Guillain-Barre, the ocular variant. Called the Miller-Fisher variant. So they can have any degree of ophthalmoplegia. My patient happened to have striking complete ophthalmoplegia. So you can have it of any sort. Unilateral, bilateral. More often bilateral. There can be ptosis, and sometimes the pupils can be affected. In the patient I showed, the pupils weren’t affected. And the patient I saw after that, the pupils were affected. Is there any factor for omission of myasthenia? Does it depend on presentation? Or antiacetylcholine? I don’t think so. There’s some evidence in the literature to suggest that if you treat someone early on with an initial diagnosis of ocular myasthenia with corticosteroids, that might prevent progression to generalized or systemic myasthenia. That’s not universally agreed, that that’s the case. And there are people who have tried to study it. There’s no study that — randomized, controlled clinical trial — that’s answered that question. So I don’t know about favors for remission. I’m trying to think. Just in my own patients. That’s a very good question, though. I don’t know that anyone’s really looked at that. And I probably could have one of my fellows retrospectively look at our patients to try to figure that out. Maybe we should study it. I don’t know the answer. And I’m not sure. I would have to do a literature search to see if there is an answer. As a subspecialty, neuroophthalmology is quite different from the others. I don’t know if I should ask my question about that now or personally. I would say personally. Since we’re running over. If you have my email, feel free to email me, if you like. 4th nerve palsy and skew deviation… So that’s a good question, that can get pretty complicated, but in general… For me to diagnose a 4th nerve palsy, I want to see all the aspects of a 4th nerve palsy. I want to see worsening with ipsilateral head tilt. I want to see torsional double vision. I want to use a double Maddox rod and measure torsion. I want the misalignment to be worse when the patient looks down. And specifically when they look down and to the right. I want it to get better. In other words, I want it to fit the pattern of a 4th nerve palsy. I see patients frequently… I think it’s a 4th nerve palsy, but it doesn’t make any difference if they look up or down. Well, that’s not the pattern of a 4th nerve palsy. Oh, sorry, skew deviation. So the think the answer is it can be tough to make that decision. In a skew deviation, most of the skews I see are pretty comitant. So if there’s a 6 prism diopter vertical misalignment in primary, it’s 6 when they look up and 6 when they look down. The other question that’s more complicated, and I don’t want to get into, is the ocular tilt reaction. That’s a whole nother story. But I think the difference to me is I’m looking for the pattern of a 4th nerve palsy. Not to say that myasthenia couldn’t — I’m sorry. A skew might not mimic it. But… That’s the way I would leave that, I think. Frequency in how to diagnose Eaton-Lambert. I didn’t mention it. The reason I didn’t mention it — this is a paraneoplastic syndrome that can mimic myasthenia. Instead of fatigability, it can improve with repetition. It’s paraneoplastic. Which means that unfortunately there is an underlying cancer that may or may not be diagnosed. Small cell lung cancer is the most common. I’ve seen it in other cancers. But in my pushing 30-year career of neuroophthalmology, I’ve seen one Eaton-Lambert syndrome. So you might get tested on it, but you probably are not gonna see it, or if you do, you’re not gonna see it much. How do we diagnose and treat myasthenia in patients with thyroid eye disease? Another good question, and it gets to the point I didn’t make, is that there is a reported — a small chance of association. Both thyroid eye disease and myasthenia are autoimmune problems. And when someone has one autoimmune problem, they’re more likely to have two. And so there is — and I think in the literature, it says maybe 5% of thyroid patients might have myasthenia. That seems very high to me. So how do you diagnose is? Very difficult. Of course, if you have someone you’re pretty sure or you know has had thyroid eye disease, and now they develop ptosis, that should not be happening with thyroid eye disease. If you see someone who you think has thyroid eye disease and they have an exotropia, that would be very unusual in thyroid eye disease. Why? Because the lateral rectus muscle is usually not affected in thyroid. And that’s the muscle that would have to be affected, because the thyroid is restrictive. That’s the muscle that would have to be affected to give you an exotropia. So if you see someone who you think has thyroid eye disease, and they’re exotropic, they may have thyroid eye disease, but they may have myasthenia as well. So of course, in that scenario, you’re going to check acetylcholine receptor antibody levels. You could do an ice test. You could do a Tensilon test if you do Tensilon tests. But sometimes that can be difficult. I think the last question — which is another good question — is is there a real effect of selenium in thyroid eye disease? I’m not sure there’s a real effect, but there is at least one study where they took patients, and I can’t quote you the article, but if you Google PubMed — selenium and thyroid eye disease, you’ll find it — where they treated patients randomly with thyroid eye disease, with placebo versus selenium. And I think the dose was I wanna say 300 milligrams BID. I could be wrong. Check that. And I do recommend selenium for patients with mild to moderate thyroid eye disease. And in the study, basically they had the patients fill out sort of a quality of life questionnaire. Gee, how bad are your eyes? Before starting the placebo or the selenium. And then they treated them for a few months, and asked them the same questions. And they did show that the patients taking selenium felt as a group — felt that there was improvement in their eye symptoms, compared to the group that were getting the placebo. So selenium, at least in the United States, is available over the counter. There’s no prescriptions. I tell patients — listen, I don’t think it’s gonna have a huge effect on bad thyroid eye disease, but in my patients who are, you know, have uncomfortable eyes, which is a lot of them, I recommend trying selenium. All right. I think that is the end of the questions. So thanks to everyone for participating and for asking the questions. I think that’s it for the ocular motility portion of our neuroophthalmology… I believe we have a couple of other potential topics coming up. One of them — there was gonna be another talk on optic neuropathies. We covered a lot of optic neuropathies in part I and part II, but there are certainly some that we didn’t really cover that could be part III. That would include things like papilledema. I’ll have to look back and see what we didn’t cover. And the other neuroophthalmology webinar in the future will be one on neuroimaging. So I thank everybody for their participation. Good to, quote-unquote, “see” everyone. Have a good day.